Oncogenes are a class of abnormal genes capable of inducing cancer. They are derived from normal genes, called proto- oncogenes, which are present in all cells. In animals, chemical carcinogens can change proto-oncogenes into oncogenes through mutation. The mutations are often chemical specific, so that a particular chemical carcinogen will induce a characteristic activating mutation within a specific proto-oncogene. The pattern of these mutations in a tumor may be an accurate marker of etiologic exposure. Oncogenes are frequently found in a variety of human cancers. Studies in the Branch have been established to investigate the role of oncogenes in the etiology of carcinogen-induced human tumors. Bladder cancer was chosen as a model tumor for this investigation, since it is perhaps the best prototype of a chemically induced human tumor. In one study, smoking and environmental exposure information is being collected on 30 patients about to undergo resection of bladder tumors. The patient's exposure will be correlated and compared with the results of oncogene assays done on portions of their resected tumor. In a second study, oncogene assays will be done on bladder tumor tissues resected from 100 individuals with occupational exposures to the potent bladder carcinogens benzidine and b-napthylamine; and compared to oncogene assays done on bladder tumor tissues resected from 100 individuals without such exposures. Individuals with exposure to these chemicals are rare, but samples of bladder tumor tissue from them are available in the form of paraffin- embedded tissue blocks made and stored following surgery. Recently, oncogene assays have been developed for use with these blocks, allowing us to determine the oncogene status of tumors resected many years ago from individuals with exposures to these powerful chemical carcinogens.